Novel generation and ring closure of 1,3-thiaza-1,3-butadiene S-oxides through thermal cycloreversion of 6H-1,3,5-oxathiazine S-oxides

Article abstract of DOI:10.1016/S0040-4039(03)00329-0

Heating of 6H-1,3,5-oxathiazine S-oxides efficiently afforded 1,2,4-oxathiazoles through the mechanism involving thermal cycloreversion of the substrates and the subsequent ring closure of the intermediary 1,3-thiaza-1,3-butadiene S-oxides.

Full text of DOI:10.1016/S0040-4039(03)00329-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 2517–2519
Novel generation and ring closure of 1,3-thiaza-1,3-butadiene
S-oxides through thermal cycloreversion of 6H-1,3,5-oxathiazine
S-oxides
Kazuaki Shimada,* Islam Md. Rafiqul, Masanobu Sato, Shigenobu Aoyagi and Yuji Takikawa
Department of Chemical Engineering, Faculty of Engineering, Iwate University, Morioka, Iwate 020-8551, Japan
Received 18 December 2002; revised 27 January 2003; accepted 31 January 2003
Abstract—Heating of 6H-1,3,5-oxathiazine S-oxides efficiently afforded 1,2,4-oxathiazoles through the mechanism involving
thermal cycloreversion of the substrates and the subsequent ring closure of the intermediary 1,3-thiaza-1,3-butadiene S-oxides.
© 2003 Elsevier Science Ltd. All rights reserved.
Immense interest has been focused on the preparation
and synthetic use of thione S-oxides in the light of their
heterocumulene-like structures and unique reactivities.
However, in spite of high potentiality of new reactive
intermediates toward various reagents, only limited
studies concerning the generation of heterodienes
cumulated with sulfine or sulfene substructures have
been achieved due to the preparative difficulties of their
precursors and the lack of suitable trapping methods of
such reactive species.1 In the course of the studies on
chalcogenocarbonyl functionalities bearing p-conjuga-
tion systems, convenient routes for the generation of
azine S-oxides 2. In this paper, we report a generation
of sulfine-type novel heterodienes B and the subsequent
facile ring closure of B to give 5H-1,2,4-oxathiazoles 3.
6H-1,3,5-Oxathiazines 1a–g were prepared as single
stereoisomers by treating an alkanethioamide or an
arenethioamide with pivalaldehyde or 2,4,6-trimethyl-
1,3,5-trioxane (paraldehyde) and BF3·OEt2.2,3 In con-
trast, all attempts for the synthesis of 1 bearing a bulky
substituent were unsuccessful. Subsequent mCPBA oxi-
dation of 1a–d in CH2Cl2 at 0°C afforded the corre-
sponding S-oxides 2a–d as single epimers in
quantitative yields. However, the relative stereochem-
istry of the newly-formed SꢀO bonds of 2a–d was not
determined through the 1H NMR experiments using
Eu(fod)3 due to the instability of 2a–d toward the
contact with Lewis acids involving NMR shift reagents.
In contrast, 2f and 2g were obtained as inseparable 3:1
epimeric mixtures and mCPBA oxidation of 1e only
gave a complex mixture.
1,3-thiaza-1,3-butadienes
A only through thermal
cycloreversion of 6H-1,3,5-oxathiazines 1 have been
reported by several authors.2 These findings just derived
us to envisage the generation of the oxygenated variants
B through an analogous route starting from 6H-1,3,5-
oxathiazine S-oxides 2. According to our expectation as
mentioned above, we started our exploration for the
preparation and thermal reactions of 6H-1,3,5-oxathi-
Keywords: 6H-1,3,5-oxathiazine S-oxide; 1,3-thiaza-1,3-butadiene S-oxide; sulfine; 5H-1,2,4-oxathiazole; 1,2,4-thiadiazole.
* Corresponding author. Tel.: +81-19-621-6324; e-mail: shimada@iwate-u.ac.jp
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00329-0

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K. Shimada et al. / Tetrahedron Letters 44 (2003) 2517–2519
Heating a CHCl3 or a benzene solution of S-oxides
2a–c at refluxing temperature for several hours afforded
the corresponding 5H-1,2,4-oxathiazoles 3a–c in almost
quantitative yields, and neither deoxygenation products
1a–c nor nitriles 6a–c were found in the crude products.
However, 3 were relatively unstable toward the storage
and the contact with silica gel and were quantitatively
converted into 3,5-diaryl-1,2,4-thiadiazoles 4a–c and
elemental sulfur in both cases. Therefore, isolation of
3a–c was carried out only through simple evacuation of
volatile pivalaldehyde at rt. Treating a CH2Cl2 solution
of 3a with p-toluenesulfonic acid (1.1 mol amt.) gave a
similar result to the reaction of 3a with silica gel. It is
noteworthy that 3,5-di-t-butyl-1,2,4-thiadiazole (5) was
not found at all through these reactions. In contrast,
heating of 2d only gave a complex mixture. When a
CDCl3 solution of 2a was kept standing in an NMR
through the route involving the formation of heterodi-
enes B followed by addition of ethanol to B and
deoxygenation of the resulting thioamide S-oxides 8.4
However, all attempts for trapping of B using 2,3-
dimethyl-1,3-butadiene, acetylenes, or allyltrimethylsi-
lane were unsuccessful.
Heating of a CDCl3 solution of 3a at 100°C for 12 h in
a sealed NMR tube gave a 1:1 mixture of nitrile 6a and
pivalaldehyde besides the formation of elemental sulfur,
and when a CHCl3 solution of 3b was treated with PPh3
(1.1 mol amt.) at rt, nitrile 6b (89%) and Ph3PꢁS (86%)
were exclusively obtained. Treatment of a CHCl3 solu-
tion of 3b with benzylamine (1.2 mol amt.) at rt for 12
h also afforded 6b (93%). In these cases, neither 1,3-
oxaza-1,3-butadiene, p-chlorobenzamide, pivalamide,
nor their N-alkyl or N-aryl derivatives were found in
the crude reaction mixtures. It is assumed that thio-
philic attack of PPh3 or benzylamine onto the sulfur
atom of 3 causes SꢀO bond fission to accelerate retro
[2+2+1]-type cycloreversion, and all these results indi-
cated the 5H-1,2,4-oxathiazole ring structure in 3 rather
than the alternative ring systems, such as 3H-1,2,4-
oxathiazoles. It was assumed that the ring system of 3
was formed through the route involving thermal ring
fission of 2 and the subsequent ring closure of 1,3-thi-
aza-1,3-butadiene S-oxides B as shown in Scheme 1.
However, 3a–c were oily matters, and mCPBA oxida-
tion of 3a–c only gave inseparable oily epimeric mix-
tures of the corresponding S-oxides 7 in approximate
3:1 ratios. Therefore, attempts for the final structural
confirmation of compounds 3 or their derivatives 7
through X-ray crystallographic analysis were not possi-
ble at this time.
1
tube and was subjected to H and 13C NMR monitor-
ing at 25°C, a gradual increasing in the intensities of the
signals of 3a and pivalaldehyde was observed along
with decreasing of the signals of 2a and almost 1:1
mixture of 3a and pivalaldehyde with a small amount
of 4a was found after standing the solution for 300 h.
Furthermore, standing of the resulting mixture for an
additional 500 h resulted in conversion into a mixture
of 4a and pivalaldehyde in a 1:4 molar ratio along with
precipitation of elemental sulfur. Contact of epimeric
mixtures of 2f or 2g with silica gel in a similar manner
also formed 4a or 4c, respectively. All results of the
thermal reactions of 2 are summarized in Table 1.
When an ethanolic solution of 2a was heated at reflux-
ing temperature for 26 h, thioamide 9a2c was obtained
in 12% yield along with 4a (35%) and unidentified
products. This result suggested that 9a was afforded
Table 1. Formation of 5H-1,2,4-oxathiazoles 3 through thermal cycloreversion of 2
Substrate
R2
Solvent
Temp. (°C)
Time (h)
Yield (%)
R1
2
3
4
R2CHO
C6H5
C6H5
C6H5
p-ClC6H4
p-FC6H4
C6H5
t-C4H9
t-C4H9
t-C4H9
t-C4H9
t-C4H9
CH3
2aa
2aa
2aa
2ba
2ca
2fd
2gd
Benzene
CDCl3
CDCl3
Benzene
Benzene
Benzene
Benzene
Reflux
rt
rt
Reflux
Reflux
Reflux
Reflux
5
300
800
6
8
5
92 (3a)
85 (3a)c
0 (3a)
93 (3b)
91 (3c)
0e
0
0b
15 (4a)c
Quant. (4a)c
0
Quant.
Quant.
0b
0
0b
50 (4a)f
53 (4c)f
0b
p-FC6H4
CH3
5
0e
0b
a A single stereoisomer.
b Aldehydes were assumed to get away during the heating.
c Estimated yields based on the integration of the 1H NMR spectrum of the reaction mixture.
d Epimeric mixture.
e Not isolated.
f An epimeric mixture of 2f or 2g was heated, and the resulting mixtures were taken in contact with silica gel. The yields of 4 were based on the
starting 1f and 1g.

K. Shimada et al. / Tetrahedron Letters 44 (2003) 2517–2519
2519
Scheme 1. Plausible pathway for the formation of 3, 4, 6, 7, and 9.
It is noteworthy that 1,2,4-thiadiazoles were
4
4435–4438; (i) Motoki, S.; Toba, Y.; Karakasa, T.; Saito,
T. Chem. Lett. 1988, 319–322; (j) Braverman, S.; van
Asten, P. F. T. M.; van der Linden, J. B.; Zwanenburg, B.
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efficiently obtained through the contact of 3 with silica
gel or a Lewis acid. Several authors reported the forma-
tion of 4 through oxidative dimerization of primary
thioamides,5 and now we can propose a plausible path-
way of conversion of 3 into 4 involving the formation
of thioamide S-oxides 10 through acid-induced
hydrolytic fragmentation of 3 and the subsequent con-
densation of 10.
In conclusion, we have found a generation of novel
sulfine-type intermediates B through thermal cyclore-
version of 6H-1,3,5-oxathiazine S-oxides 2 and a facile
ring closure of B into 5H-1,2,4-oxathiazoles 3. Further
attempts for the expansion of the generation method to
other oxidized variants of 1,3-thiaza-1,3-butadienes
through a similar route starting from 1 are in progress
in our laboratory.
2. (a) Burger, K.; Albanbauer, J.; Eggersdorfer, M. Angew.
Chem. 1975, 87, 816–817; (b) Giordano, C.; Belli, A.; Abis,
L. Tetrahedon Lett. 1979, 20, 1537–1538; (c) Shimada, K.;
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C. Chem. Lett. 1997, 701–702; (d) Shimada, K.; Aikawa,
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3. Giordano, C.; Belli, A. Synthesis 1975, 789–791.
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This work was partially supported by The Foundation
for Japanese Chemical Research (333(R)).
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